tumor cells stimulates immunity against both the allogeneic MHC 
gene on transduced cells as well as previously unrecognized 
antigens in unmodified tumor cells (5) . The introduction of an 
allogeneic MHC gene directly into tumors in vivo has induced 
partial tumor regressions, as well as the specific cytotoxic T 
cell response to other antigens. In a recent trial in humans, we 
observed no toxicity of this form of treatment. We have 
continued to optimize this gene delivery approach, and now 
propose four improvements on the previous protocol which could 
improve its ultimate efficacy. These modifications include 1) 
the use of another cationic lipid formulation, DMRIE/DOPE, 2) 
optimization of vector expression and inclusion of a cytokine 
gene, 3) catheter-mediated gene delivery, and 4) application to 
different tumor types. 
Because this approach employs direct gene transfer in vivo, 
it can be applied easily in a clinical setting to spontaneously 
arising tumors, alone or in combination with cytokines or other 
adjuvant treatments, including adoptive lymphocyte transfer, to 
augment tumor immunity. In this study, we propose another phase 
I clinical trial almost identical to our previous protocol which 
will evaluate the safety and appropriate dosage for these new 
modifications. Recombinant gene expression in vivo will be 
documented, and the specificity and mechanism of the immune 
response will be characterized. Escalating treatment regimens 
will be used and tumor growth evaluated. These studies will 
define the safety of the modifications of this approach to the 
immunotherapy of malignancy and may provide therapeutic effects 
[706] 
Recombinant DNA Research, Volume 17 
